What Are Viral Vectors, and How Are They Used in Gene Therapy?
Key takeaways:
Some gene therapies use viruses — known as viral vectors — to deliver genetic material into your cells.
The most common viruses used in viral vectors are adenovirus, adeno-associated virus, or lentivirus. These viruses are inactivated, and do not cause infections when used in gene therapy.
Viral vectors have some risks. It’s possible that your immune system reacts to the virus and causes inflammation.
Your genes are what make you unique. They’re responsible for your particular traits, like your hair color and even aspects of your personality. Genes are passed on from parents to children. In some cases, an altered (mutated) or missing gene can put you at higher risk for disease.
Scientists have been finding ways to make specific changes to our genes for decades. This is known as gene therapy. With gene therapy, mutated or missing genes can be altered or replaced in an attempt to cure or treat a medical condition, like cancer or genetic disorders.
Some gene therapy medications use viruses during the treatment process. This may sound unusual since most people associate viruses with infections, like the common cold or the flu. But the way viruses function make them a useful tool for gene therapy.
Viruses multiply by inserting their genetic material into human cells. Once a human cell is infected, it can then infect other cells, which allows the virus to spread throughout the body. So, some gene therapies then use viruses to provide your cells with specific genetic material as a form of treatment. When used in this way, they’re called viral vectors.
In this article, we’ll discuss how viral vectors work in gene therapy and how they help treat certain diseases.
What are viral vectors?
First, let’s think about what’s needed for gene therapy to be successful. Different medical conditions — like cystic fibrosis and some cancers — are caused by specific gene mutations in cells. To treat or cure disease, gene therapy must reach the mutated cells.
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Imagine it like this: gene therapy is loaded onto a delivery truck and delivered to the part of the body that needs treatment. This “delivery truck” is called a vector. Viral vectors are one type of vector. They’re made of a modified virus that can’t cause disease.
Viral vectors are useful because they’re naturally good at entering human cells. In 2017, the FDA approved the first gene therapy available in the U.S., Kymriah (tisagenlecleucel). It’s approved to treat a form of acute lymphoblastic leukemia (ALL) and certain types of non-Hodgkin lymphoma (NHL).
Kymriah uses a person’s own cells — a type of white blood cells called T cells — to treat ALL. The T cells are genetically modified with a specific protein that directs them to kill cancer cells. This is known as CAR T-cell therapy. In CAR T-cell therapy, viral vectors carry the genetic material into a person’s T-cells.
Are viral vectors only used in gene therapy?
No. They’ve also been used to make viral vector vaccines, including Johnson & Johnson’s COVID-19 vaccine.
This vaccine uses an inactivated form of adenovirus as its viral vector. The vector helps deliver instructions to our cells to make a protein that’s unique to the COVID-19 virus. This protein is called the COVID-19 spike protein. Our cells make copies of the spike protein, which helps us remember how to fight the COVID-19 virus if we’re infected in the future.
What’s the difference between viral and nonviral vectors?
Unlike viral vectors, nonviral vectors don’t use viruses to deliver healthy genetic material. Instead, nonviral vectors — a different brand of delivery trucks — deliver genes into cells in two other ways:
Physical techniques. These include methods like needles, electric pulses, or ultrasounds to deliver new genetic material to cells.
Chemical techniques. Natural or human-made materials can be used to carry genetic material into the body. Fat molecules (lipids) are one example of this.
Are viral or nonviral vectors preferred?
There is no single type of vector that can deliver genes to all types of cells. This is why different therapies may use different types of vectors.
Viral vectors only contain a portion of the original virus — the part that delivers genetic materials. The part of the virus that causes infection is removed. But viral vectors can still cause inflammation. More on this later when we discuss the risks of viral vectors.
Compared to viral vectors, nonviral vectors may provide the following benefits:
Less potential to cause disease (pathogenicity)
Easier to produce
Less expensive to produce
But nonviral vectors are sometimes not as efficient as viral vectors in delivering genetic materials. This is why researchers study both types of vectors for different gene therapies.
What viral vectors are used in gene therapy?
Currently, all FDA-approved gene therapy medications use a type of viral vector. Remember that viral vectors don’t cause disease — only modified parts of the virus that aren’t infectious are used. The three most common viral vectors use the following viruses:
Adenovirus. This is a common virus that causes cold symptoms. Many clinical trials are studying gene therapies using adenoviral vectors. And vaccines to treat infections like Ebola, malaria, and tuberculosis are being studied using adenoviral vectors.
Adeno-associated viruses (AAV). These are small viruses that infect humans and primates (like monkeys). Zolgensma (onasemnogene abeparvovec) is a gene therapy product that treats spinal muscular atrophy using AAV as a viral vector.
Lentivirus. This is a family of viruses that includes human immunodeficiency virus (HIV). Lentivirus is a type of retrovirus. Abecma (idecabtagene vicleucel) is a gene therapy product that uses a lentivirus vector to treat multiple myeloma.
Which viral vector is best for gene therapy?
There isn’t one single viral vector that works for all gene therapies. About half of the clinical trials on gene therapy using viral vectors are studying adenoviral vectors. The other 50% are split between AAV vectors and lentivirus vectors.
Each viral vector has its unique set of challenges. Some of these challenges include:
Adenovirus is a common virus that infects humans. This means that many people may have immunity against adenovirus, causing the viral vector to be less effective.
AAV may cause a strong response from the immune system. This can make it challenging to find the right amount of AAV to use as a viral vector.
Lentivirus may have unwanted effects on other cells in the body. Lentivirus provides genetic materials in both dividing cells and non-dividing cells. This can cause unintentional effects on other cells.
What are the risks of viral vectors in gene therapy?
Our immune system is designed to protect us from different infections, including viruses. This is what makes using viral vectors for gene therapy challenging. Viral vectors must first overcome our immune system’s different lines of defense.
It’s possible that our immune system responds negatively to viral vectors. Our body may recognize it as a threat, and attempt to “clear” the virus. This process is known as immunogenicity, and it can cause unwanted side effects.
For instance, people receiving CAR T-cell therapy may develop cytokine release syndrome (CRS). CRS occurs when the immune system produces a large amount of cytokines (a type of inflammatory protein). Your body becomes overwhelmed with inflammation and the following symptoms may occur:
Fast heartbeat
Difficulty breathing
CRS can be life-threatening. It’s why some gene therapies — such as Kymriah — have a boxed warning (the most serious type of FDA warning) and a REMS program (a medication safety program) for CRS. People receiving CAR T-cell therapies should discuss this risk with their healthcare providers. In some cases, medications like corticosteroids or Actemra (tocilizumab) are needed to treat CRS.
Viral vectors may also have other safety concerns, such as:
Providing genetic materials that alter “normal” genes
Activating genes that cause cancer
Causing genetic mutations
These safety concerns can make developing gene therapies challenging. The FDA offers guidance for drug companies to ensure that these therapies are both safe and effective.
The bottom line
Gene therapy has the potential to treat and cure some medical conditions, like cancer and genetic disorders. In gene therapy, specific changes are made to human DNA by replacing mutated genes or adding or altering genes.
Viruses, known as viral vectors, are one way that genetic material can be delivered to cells in the body. The most commonly used viral vectors are adenovirus, AAV, and lentivirus. Viral vectors work well in gene therapy, but also have some risks. It’s possible that your immune system reacts to the virus and causes inflammation. Researchers are continuing to study how viral vectors can be safely used to treat different diseases.
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References
American Cancer Society. (2022). CAR T-cell therapy and its side effects.
Bouard, D., et al. (2009). Viral vectors: From virology to transgene expression. British Journal of Pharmacology.
Brudno, J. N., et al. (2019). Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management. Blood Reviews.
Bulcha, J. T., et al. (2021). Viral vector platforms within the gene therapy landscape. Signal Transduction and Targeted Therapy.
Celgene Corporation. (2021). Abecma® (idecabtagene vicleucel), suspension for intravenous infusion. Bristol Squibb Myers.
Centers for Disease Control and Prevention. (2019). Adenovirus.
Chen, H., et al. (2019). Management of cytokine release syndrome related to CAR-T cell therapy. Frontiers of Medicine.
David, R. M., et al. (2017). Viral vectors: The road to reducing genotoxicity. Toxicological Sciences.
Finer, M., et al. (2017). A brief account of viral vectors and their promise for gene therapy. Gene Therapy.
Food and Drug Administration. (2017). FDA approval brings first gene therapy to the United States.
Food and Drug Administration. (2017). What is gene therapy? How does it work? .
Food and Drug Administration. (2021). Cellular and gene therapy guidances.
Genehome. (n.d.). Vectors: Tools for gene delivery.
Gonçalves, G. A. R., et al. (2017). Gene therapy: Advances, challenges and perspectives. Einstein (São Paulo).
Goswami R., et al. (2019). Gene therapy leaves a vicious cycle. Frontiers in Oncology.
Labbé, R. P., et al. (2021). Lentiviral vectors for T cell engineering: Clinical applications, bioprocessing and future perspectives. Viruses.
Mazor, R. (2020). Immunogenicity of gene therapy products. U.S. Food and Drug Administration.
MedlinePlus. (2021). How does gene therapy work? National Library of Medicine.
Mellott, A. J., et al. (2013). Physical non-viral gene delivery methods for tissue engineering. Annals of Biomedical Engineering.
Mendonça, S. A., et al. (2021). Adenoviral vector vaccine platforms in the SARS-CoV-2 pandemic. npj Vaccines.
Milone, M. C., et al. (2018). Clinical use of lentiviral vectors. Leukemia.
National Cancer Institute. (n.d.). Chimeric antigen receptor.
National Cancer Institute. (n.d.). Cytokine release syndrome.
National Cancer Institute. (n.d.). T cell.
National Human Genome Research Institute. (n.d.). Gene.
National Human Genome Research Institute. (n.d.). Mutation.
Nayerossadat, N., et al. (2012). Viral and nonviral delivery systems for gene delivery. Advanced Biomedical Research.
Novartis Pharmaceuticals Corporation. (2021). Kymriah REMS.
Ramamoorth, M., et al. (2015). Non viral vectors in gene therapy- an overview. Journal of Clinical and Diagnostic Research.
Shirley, J. L., et al. (2020). Immune responses to viral gene therapy vectors. Molecular Therapy.
Sinclair, A., et al. (2018). Gene therapy: An overview of approved and pipeline technologies. CADTH Issues in Emerging Health Technologies.
Thaci, B., et al. (2011). The challenge for gene therapy: Innate immune response to adenoviruses. Oncotarget.
Ura, T., et al. (2014). Developments in viral vector-based vaccines. Vaccines.
Verdera, H. C., et al. (2020). AAV vector immunogenicity in humans: A long journey to successful gene transfer. Molecular Therapy.
Wang, D., et al. (2019). Adeno-associated virus vector as a platform for gene therapy delivery. Nature Reviews. Drug Discovery.
Warnock, J. N., et al. (2011). Introduction to viral vectors. Methods in Molecular Biology.
Wold, W. S., et al. (2013). Adenovirus vectors for gene therapy, vaccination and cancer gene therapy. Current Gene Therapy.
Wolff, J. A., et al. (2008). Breaking the bonds: Non-viral vectors become chemically dynamic. Molecular Therapy.
Zhang, J. M., et al. (2007). Cytokines, inflammation, and pain. International Anesthesiology Clinics.
